RESUMEN
A 45-year-old woman with neurofibromatosis type 1 (NF1) developed a tumor in the left frontal lobe that showed features of giant cell glioblastoma (GC-GB). In addition to the typical GC-GB features, the tumor showed lipogenic differentiation, with many atypical lipoblasts and mature adipocytes. Tumor cells, including the lipogenic cells, were immunoreactive for GFAP, S-100 protein, ATRX, and p53. They were negative for IDH1-R132H, BRAF V600E, synaptophysin, NeuN, p16, mismatch repair proteins, and CD34. The patient is free from recurrence at approximately two years postoperatively. This is the fifth reported case of NF1-associated GC-GB (the second adult case). NF1 gene mutation might have played a role in the pathogenesis of lipogenic differentiation of GC-GB. The differential diagnosis of lipidized GC-GB from gliosarcoma or anaplastic pleomorphic xanthoastrocytoma is briefly discussed.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Neurofibromatosis 1 , Humanos , Glioblastoma/patología , Glioblastoma/genética , Femenino , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Persona de Mediana Edad , Neurofibromatosis 1/patología , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/genética , Diferenciación Celular , LipogénesisRESUMEN
OBJECTIVE: A case of low-grade glioma in which 5-aminolevulinic acid (5-ALA) fluorescence was visualized by a digital exoscope is presented. CASE PRESENTATION: A 14-year-old girl with recurrent paroxysmal episodes of a strange smell and nausea underwent magnetic resonance imaging (MRI) for further investigation. The MRI showed a tumor with an enhanced nodule in the right temporal lobe. The patient received 5-ALA preoperatively, and intraoperative observation using a 4 K-3-dimension digital exoscope (Olympus ORBEYE) showed that the tumor was fluorescent, which was useful in determining the extent of tumor removal. Postoperative MRI showed that the tumor was completely removed. The histopathological diagnosis was pleomorphic xanthoastrocytoma. She was discharged without any complications. CONCLUSIONS: 5-ALA-fluorescence-guided resection of low-grade glioma using the ORBEYE was useful for determining the extent of removal.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Cirugía Asistida por Computador , Femenino , Humanos , Niño , Adolescente , Ácido Aminolevulínico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Glioma/diagnóstico por imagen , Glioma/cirugía , Glioma/patología , Astrocitoma/cirugía , Cirugía Asistida por Computador/métodosRESUMEN
PURPOSE: A rare case of a newborn girl born by a normal vaginal delivery who developed a severe supratentorial subdural hematoma due to a laceration in the tentorium cerebelli is presented. METHODS AND RESULTS: The girl, born by normal vaginal delivery at 39 weeks and 4 days of gestation, showed an intermittent decrease in oxygen saturation and bulging of the anterior fontanelle. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a subdural hematoma centered in the left occipital region with a midline shift. Hematoma evacuation with craniotomy was performed, and the source of bleeding was a laceration of the tentorium cerebelli. CONCLUSION: Severe supratentorial subdural hematomas can occur due to laceration of the tentorium cerebelli even in a normal vaginal delivery.
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Laceraciones , Recién Nacido , Femenino , Humanos , Hematoma Subdural , Duramadre , Tomografía Computarizada por Rayos X , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Although there have been reports investigating the quality of life of patients who underwent ventriculoperitoneal shunting or endoscopic third ventriculostomy (ETV) for congenital hydrocephalus, there have been no studies of the quality of life of patients after ventriculoperitoneal shunt (VPS) removal. In the present study, a survey of pediatric and congenital hydrocephalus patients was conducted to compare the quality of life of patients with a remaining VPS with that of patients who had the shunt removed. METHODS: Between February 2020 and November 2021, an outpatient survey was administered to patients 8 years of age and older who had undergone VPS due to a diagnosis of congenital hydrocephalus. The Hydrocephalus Outcome Questionnaire (HOQ) was used to assess the quality of life for this study. The HOQ scores (overall health score, physical health score, cognitive health score, and social-emotional health score) were compared among three groups: a VPS-remaining group, VPS-removed with endoscopic third ventriculostomy (ETV) group, and VPS-removed without ETV group. RESULTS: The total number of patients who underwent VPS for hydrocephalus was 71, with 47 in the VPS-remaining group, 14 in the shunt-removed with ETV group, and 10 in the shunt-removed without ETV group. The HOQ overall health score was 0.68 for the VPS-remaining group, 0.74 for the shunt-removed with ETV group, and 0.74 for the shunt-removed without ETV. There were no significant differences between the VPS-remaining group and the VPS-removed with or without ETV groups (p = 0.3255, 0.4178, respectively). CONCLUSION: There was no significant difference in the quality of life between patients with a remaining VPS and those who had their VPS removed with or without ETV.
Asunto(s)
Hidrocefalia , Neuroendoscopía , Tercer Ventrículo , Humanos , Niño , Calidad de Vida , Neuroendoscopía/efectos adversos , Resultado del Tratamiento , Hidrocefalia/etiología , Ventriculostomía/efectos adversos , Derivación Ventriculoperitoneal/efectos adversos , Tercer Ventrículo/cirugíaRESUMEN
BACKGROUND: Little is known about the real-world status of neurosurgical treatment of myelomeningocele patients. OBJECTIVE: To investigate the real-world status of neurosurgical treatment of myelomeningocele patients, medical claims data provided by the Japan Medical Data Center (JMDC) were analyzed. METHODS: The health claims data of 556 patients with myelomeningoceles from January 2005 to March 2020 were examined. The number of neurosurgical procedures, including myelomeningocele repair, tethered cord release, cerebrospinal fluid (CSF) shunt, CSF drainage, and endoscopic third ventriculostomy (ETV), was determined. RESULTS: A total of 313 neurosurgical procedures were performed for 135 patients in 74 institutions during the study period. The shunt survival rate was most affected by shunts that were revised when the patient was less than 1 year old, which had a significantly lower survival rate than all of the initial shunts performed when the patient was less than on1 year old; the 1-year shunt survival rate was 35 vs 64% (P = 0.0102). The survival rate was significantly lower in patients younger than 1 year who had CSF drainage before shunting compared to those younger than 1 year who did not have CSF drainage before shunting; the 1-year shunt survival rate was 27 vs 59% (P = 0.0196), and 81% of patients remained free of tethered cord release 10 years later. CONCLUSIONS: In this study, a revised shunt of less than 1 year of age and CSF drainage before shunting were the factors that lowered the shunt survival rate in the real world for CSF shunts for hydrocephalus associated with myelomeningocele.
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Hidrocefalia , Meningomielocele , Defectos del Tubo Neural , Tercer Ventrículo , Lactante , Humanos , Meningomielocele/complicaciones , Meningomielocele/cirugía , Japón , Tercer Ventrículo/cirugía , Derivaciones del Líquido Cefalorraquídeo/métodos , Ventriculostomía/métodos , Hidrocefalia/cirugía , Hidrocefalia/complicaciones , Procedimientos Neuroquirúrgicos , Defectos del Tubo Neural/cirugía , Pérdida de Líquido Cefalorraquídeo/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Stable intraoperative neurophysiology monitoring of infants, especially very young infants, is challenging. In this study, motor evoked potentials (MEPs), the bulbocavernosus reflex (BCR), and somatosensory evoked potentials (SEPs) were simultaneously monitored in infants with lumbosacral lipomas, and these methods were compared retrospectively. METHODS: A total of 21 surgeries performed for lumbosacral lipoma in patients less than 1 year old were studied. The mean age at surgery was 133.8 days (range 21-287 days; ≤ 120 days: 9 cases, > 120 days: 12 cases). Transcranial MEPs were measured in the anal sphincter and gastrocnemius, and tibialis anterior and other muscles were added as needed. The BCR was measured by the electromyogram of the anal sphincter muscle with stimulation of the pubic region, and SEPs were measured from the waveforms of stimulation of the posterior tibial nerves. RESULTS: For the BCR, stable potentials could be recorded for all 9 cases at ≤ 120 days of age. In contrast, for MEPs, stable potentials could be recorded in only 4 of 9 cases (p < 0.05). For all patients > 120 days of age, MEPs and the BCR were measurable. SEPs were undetectable in some patients regardless of age. CONCLUSION: The BCR could be more consistently measured than MEPs in infant patients with lumbosacral lipoma at ≤ 120 days of age.
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Monitorización Neurofisiológica Intraoperatoria , Lipoma , Neoplasias de la Columna Vertebral , Humanos , Lactante , Monitorización Neurofisiológica Intraoperatoria/métodos , Estudios Retrospectivos , Potenciales Evocados Motores , Potenciales Evocados Somatosensoriales/fisiología , Lipoma/cirugíaRESUMEN
AIM: The usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-assisted surgery for maximum resection of malignant gliomas has been established. However, its usefulness when combined with endoscopic surgery for deep-seated tumors has not been well established. In this study, whether 5-ALA photodynamic diagnosis (PDD) is feasible and useful for endoscopic surgery was investigated. METHODS: A specially designed endoscope for PDD that delivers white light or blue light (375-440 nm) as excitation light was used. The fluorescence emitted by the tumor was evaluated in the cavity during resection or at the tip of the sheath during biopsy. The intensity of fluorescence was classified into three categories: strong, vague, and negative. RESULTS: A total of 30 intraparenchymal tumors were observed with a neuroendoscope and 5-ALA PDD; 16 patients underwent resection, and 14 underwent biopsy. Overall, 67% (20/30) of tumors showed positive fluorescence of protoporphyrin IX. High-grade gliomas (HGGs) including glioblastoma (GBM) and anaplastic astrocytoma (AA) showed strong fluorescence in 47% (7/15), vague fluorescence in 33% (5/15), and negative fluorescence in 20% (3/15) of cases. Low-grade gliomas (LGGs) showed vague fluorescence in 33% (1/3) and negative fluorescence in 67% (2/3). Diffuse large B-cell lymphoma (DLBCL) showed vague fluorescence in 38% (3/8) and negative fluorescence in 63% (5/8). Metastatic tumors showed strong fluorescence in 25% (1/4) and vague fluorescence in 75% (3/4). In the comparison of fluorescence evaluation, a significant difference was observed only in the comparison between HGGs and DLBCL (p = 0.049). CONCLUSION: These results suggest that 5-ALA PDD-assisted endoscopic surgery is feasible and useful for deep-seated intraparenchymal tumors.
RESUMEN
BACKGROUND: In order to remove a foreign body in the ventricle, such as a ventricular drainage catheter, craniotomy and corticotomy are required to access the ventricle. A case in which a catheter in the 4th ventricle was safely removed with a flexible neuroendoscope is reported. CASE DESCRIPTION: A 47-year-old man underwent coil embolization and ventricular drainage for subarachnoid hemorrhage. 10 days after the operation, he tore off the ventricular drainage catheter and the catheter remained intracranially. The tip of the catheter was in the 4th ventricle and the operation to remove remaining catheter with a neuroendoscope was performed. Using a neuroendoscope, we could remove the catheter safely and did not detect the complications. CONCLUSION: To date, there have been no reports of cases in which a drainage catheter in the ventricle was removed using a flexible endoscope. This case suggests that a flexible endoscope is useful for removing a foreign body from the ventricle less invasively.
Asunto(s)
Cuerpos Extraños , Hidrocefalia , Neuroendoscopía , Masculino , Humanos , Persona de Mediana Edad , Neuroendoscopios , Cuarto Ventrículo/diagnóstico por imagen , Cuarto Ventrículo/cirugía , Derivación Ventriculoperitoneal/efectos adversos , Catéteres , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Hidrocefalia/cirugíaRESUMEN
Resection or biopsy of intraventricular brain tumors using an endoscope has become common, but the limitations of these procedures are not clear. Manipulation to access a tumor that arises from the blind angle of the rigid endoscope, such as the anterior part of the aqueduct, is limited. We report here that we successfully resected a recurrent medulloblastoma in the anterior part of the aqueduct using only a flexible endoscope. This method appears to be suitable for poorly vascularized and suctionable tumors that arise in the blind angle of a rigid endoscope.
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Neoplasias Encefálicas , Neoplasias Cerebelosas , Meduloblastoma , Neuroendoscopía , Neoplasias Cerebelosas/diagnóstico por imagen , Neoplasias Cerebelosas/cirugía , Acueducto del Mesencéfalo , Humanos , Meduloblastoma/diagnóstico por imagen , Meduloblastoma/cirugíaRESUMEN
Medulloblastoma is the second-most common malignant tumor in children. Medulloblastoma has been categorized into four distinct molecular subgroups: WNT, sonic hedgehog (SHH), group 3, and group 4. We report on a male child with medulloblastoma, in whom an enlarged ventricle was diagnosed in utero. Magnetic resonance imaging showed cyst formation in the cerebellar hemisphere initially, with tumor growth being indicated later. Tumor resection was performed when the boy was 12 months old. The histological findings showed extensive nodularity. Further genetic analysis revealed the tumor to be SHH type. This is the first description of a medulloblastoma observed from the fetal stage. Our findings in this case indicate that cyst formation may be the pre-neoplastic lesion of SHH-subtype medulloblastomas.
Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Neoplasias Cerebelosas/diagnóstico por imagen , Neoplasias Cerebelosas/cirugía , Cerebelo/metabolismo , Niño , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Meduloblastoma/diagnóstico por imagen , Meduloblastoma/cirugíaRESUMEN
PURPOSE: Lipoma of the filum terminale (FL) is an abnormality in which fat is deposited in the filum terminale. This lipoma is often detected by skin abnormalities in the lumbosacral area such as a sacrococcygeal dimple. Some cases may develop tethered cord and become symptomatic. However, the genetic basis of FL is still unclear. METHODS: This study aimed to determine whether there was a family history of FL or other forms of spina bifida among 54 families of 56 patients with FL and to examine whether there is a familial predisposition in FL. In addition, sex, age at diagnosis, presence of symptoms, presence of sacrococcygeal dimple, and the level of conus medullaris between familial and spontaneous cases were evaluated. RESULTS: Of the 54 families of FL patients, there were 48 siblings. Among the 48 siblings, 2 had "occult" FL. The frequency of FL among siblings was estimated to be 4.2% (2/48), which was significantly higher than the sum of previously reported cases of spontaneous FL (0.91%; p = 0.017). However, there was no significant difference in sex, age at diagnosis, presence of symptoms, presence of sacrococcygeal dimple, diameter of filum terminale, or level of conus medullaris between familial and spontaneous cases. CONCLUSION: To our knowledge, this is the first report on familial FL and examination of the frequency of FL among siblings. The high probability of FL among siblings of FL patients suggests that genetic factors may play a role in FL development.
Asunto(s)
Cauda Equina , Lipoma , Defectos del Tubo Neural , Cauda Equina/diagnóstico por imagen , Humanos , Lipoma/genética , Imagen por Resonancia Magnética , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/genética , Médula EspinalRESUMEN
PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Interferón beta/uso terapéutico , Temozolomida/uso terapéutico , Adulto , Anciano , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Telomerasa/genética , Resultado del Tratamiento , Proteínas Supresoras de Tumor/genética , Adulto JovenRESUMEN
PURPOSE: This study explored the superiority of temozolomide (TMZ) + interferonß (IFNß) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100-200 mg/m2/day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNß + RT arm intravenously received IFNß (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). RESULTS: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNß + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNß + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. CONCLUSIONS: TMZ + IFNß + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Interferón beta/uso terapéutico , Temozolomida/uso terapéutico , Administración Intravenosa , Adulto , Anciano , Antineoplásicos/efectos adversos , Neoplasias Encefálicas/mortalidad , Quimioradioterapia , Femenino , Glioblastoma/mortalidad , Humanos , Interferón beta/efectos adversos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Temozolomida/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.
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Neoplasias Encefálicas/genética , Germinoma/genética , Transducción de Señal/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Inestabilidad Cromosómica/genética , Metilación de ADN , Análisis Mutacional de ADN , Femenino , Células Germinativas , Humanos , Lactante , Japón , Elementos de Nucleótido Esparcido Largo/genética , Masculino , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Mutación , Fosfatidilinositol 3-Quinasas/genética , ARN Mensajero/metabolismo , Estadísticas no Paramétricas , Adulto JovenRESUMEN
5-Aminolevulinic acid (5-ALA) fluorescence-guided surgery is widely used for detection and planning of resection of malignant gliomas and other brain tumors. However, no reports have described 5-ALA fluorescence-guided surgery or direct visualization of germ cell tumors. Here, we report two cases of germ cell tumors in which a positive 5-ALA fluorescent signal was visualized with a neuroendoscope. Both cases had a tumor in the pineal region that was associated with hydrocephalus. The patients underwent surgery after administration of 5-ALA. After ventricular puncture of the anterior horn, we could observe the ventricular wall and tumor using the Karl Storz Photodynamic diagnosis system endoscope. Then, biopsy of the pineal tumor and endoscopic third ventriculostomy were performed in both cases. In case 1, a 22-year-old man, part of the ventricular wall and tumor tissue showed red fluorescence. In case 2, a 16-year-old man, part of the fornix and infundibular recess showed red fluorescence, and the tumor showed relatively weak red fluorescence. The histopathological diagnosis of both cases was pure germinoma. This is the first report of direct visualization of mixed germinomas with 5-ALA fluorescence-guided endoscopic surgery. This method not only allows visualization of the tumor mass, but may also be useful for detailed observation in the ventricular wall.
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Ácido Aminolevulínico/uso terapéutico , Endoscopía/métodos , Fluorescencia , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Adolescente , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Adulto JovenRESUMEN
Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined. Tumor formation was evaluated using intracranial xenograft models. The effect of temozolomide was measured in vitro by cell viability assays. We established the neuroendocrine tumor sphere cell line ANI-27S, which displayed stable exponential growth, virtually unlimited expansion in vitro, and expression of stem-cell markers such as CD133, nestin, Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the neuroendocrine markers synaptophysin and chromogranin A. Intracranial xenotransplanted brain tumors recapitulated the original patient tumor and temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first time, we demonstrated the presence of a sphere-forming, stem cell-like population in brain metastases from a primary neuroendocrine tumor. We also demonstrated the potential therapeutic effects of temozolomide for this disease.
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Antineoplásicos Alquilantes/farmacología , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Células Madre Neoplásicas/patología , Tumores Neuroendocrinos/tratamiento farmacológico , Esferoides Celulares/patología , Antígeno AC133/genética , Antígeno AC133/metabolismo , Anciano , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Supervivencia Celular/efectos de los fármacos , Cromogranina A/genética , Cromogranina A/metabolismo , Dacarbazina/farmacología , Humanos , Masculino , Ratones , Trasplante de Neoplasias , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Nestina/genética , Nestina/metabolismo , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Cultivo Primario de Células , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Sinaptofisina/genética , Sinaptofisina/metabolismo , Temozolomida , Células Tumorales CultivadasRESUMEN
Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.
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Neoplasias del Sistema Nervioso Central/genética , Mutación/genética , Neoplasias de Células Germinales y Embrionarias/genética , Serina-Treonina Quinasas TOR/genética , Neoplasias Testiculares/genética , Neoplasias del Sistema Nervioso Central/patología , Femenino , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/terapia , Fosfatidilinositol 3-Quinasas/genética , Recurrencia , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Testiculares/terapiaRESUMEN
A 33-year-old male presented with an extremely rare case of intraorbital fat necrosis. A magnetic resonance imaging scan showed a 10-mm mass lesion within the right lateral rectal muscle. Surgical removal was performed. Histological analysis showed diffuse adipose cells surrounded by macrophage cells. Fat necrosis was diagnosed.
Asunto(s)
Necrosis Grasa/cirugía , Neoplasias Orbitales/cirugía , Adulto , Necrosis Grasa/diagnóstico , Necrosis Grasa/etiología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Neoplasias Orbitales/complicaciones , Neoplasias Orbitales/diagnóstico , Neoplasias Orbitales/patología , Resultado del TratamientoRESUMEN
A case of diffuse midline glioma (DMG), H3 K27-altered, that arose in the right thalamus of a 14-year-old boy is reported. The patient died of tumor spread after a progressive clinical course of approximately 13 months. Histopathologically, the tumor consisted of a mixture of loose proliferation of stellate cells and compact fascicular growth of spindle cells showing a "piloid" feature. Aggregates of globular structures composed of entangled fine glial fibrils ("glio-fibrillary globules, GFGs") were observed. Tumor cells were immunoreactive for S-100 protein and glial fibrillary acidic protein (GFAP), and showed nuclear immunoreactivity for histone H3 K27M and loss of expression of H3 K27me3. Tumor cell nuclei were also negative for alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX) and p16. Although GFGs morphologically resembled "neuropil-like islands" or "neurocytic rosettes" seen in glial or glio-neuronal tumors, they showed immunoreactivity for GFAP, but not for synaptophysin. A GFG is a unique structure that has been described in DMG, H3 K27-altered, by a few investigators. To the best of our knowledge, this structure has not previously been reported in other glial or glio-neuronal tumors. It could be added as a new feature in the histopathological variations of DMG, extending its morphological spectrum. Familiarity with this feature can help prevent misdiagnosis of DMG.